By Matthew E. Fink, MD
Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, NYP/Weill Cornell Medical College
SOURCE: Shah VA, Thompson RE, Yenokyan G, et al. One-year outcome trajectories and factors associated with functional recovery among survivors of intracerebral and intraventricular hemorrhage with initial severe disability. JAMA Neurol 2022;79:856-868.
Intracerebral hemorrhage (ICH) continues to be a major cause of mortality and long-term disability. There is a 30-day case fatality rate of more than 40%, and most survivors are left with permanent disabilities. As a result, early in the course of this severe disease prognosis is based on early characteristics, and care may be withdrawn at an early stage. The natural history and long-term recovery of survivors is uncertain because of early withdrawal of care, resulting in a “self-fulfilling prophecy.”
Shah et al analyzed data that were collected from two large prospective cerebral hemorrhage treatment trials, CLEAR-III and MISTIE-III, to assess one-year recovery of function and predictors of recovery in patients who experienced a poor outcome at 30 days after ICH occurred.1,2 Because these studies required ongoing supportive treatment to assess long-term recovery, it was a selected population that would allow evaluation and determination of factors that could affect long-term recovery.
This was a post-hoc analysis of all individual patient data from the two aforementioned studies. Of 999 patients enrolled in the study, 724 survived, with a 30-day modified Rankin Scale (mRS) score of 4 or 5. After exclusion of patients for lack of follow-up data, the final cohort included 715 patients. CLEAR-III participants were randomized to intraventricular alteplase vs. placebo as treatment. MISTIE-III patients were randomized to stereotactic thrombolysis vs. standard medical treatment.
The primary outcome was the mRS score at one year. Patients were divided into good outcome (mRS 0 to 3) vs. poor outcome (mRS 4 to 6) at one year. The authors used multivariate regression models to assess hospital events and other factors that might influence recovery. Fifty-eight percent of patients were men, and the mean age was 60.3 years. The patients were diverse regarding race and ethnicity. At the end of one year, 18% had died and 43% achieved an mRS of 0 to 3.
In an adjusted model for the entire cohort, the important variables that affected mortality and poor outcome were the presence of diabetes, high National Institutes of Health Stroke Scale score, severe white matter disease, early shift of the pineal gland on imaging, acute ischemic stroke complications, need for a gastrostomy, and persistent hydrocephalus by day 30. These factors were associated with lack of recovery at one year. Factors that predicted a good outcome were resolution of the brain hemorrhage and intraventricular hemorrhage by day 30.
In the CLEAR-III cohort, poor outcome was associated with a cerebral perfusion pressure less than 60 mmHg, sepsis, and prolonged mechanical ventilation. The need for intracranial pressure monitoring was an additional factor associated with poor outcome.
The important finding here is that, of patients who had severe disability at 30 days, 40% recovered to a good outcome by one year. It is important to avoid giving a poor prognosis early in the clinical course, and to continue supportive care until the long-term outcome truly is understood.
REFERENCES
1. Hanley DF, Lane K, McBee N, et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: Results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet 2017;389:603-611.
2. Hanley DF, Thompson RE, Rosenblum M, et al. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): A randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 2019;393:1021-1032.
It is important to avoid giving a poor prognosis early in the clinical course, and to continue supportive care until the long-term outcome truly is understood.
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